TY  - EJOU
AU  - Chen, Yi-Tzu 
AU  - Kao, Shao-Hsuan 
AU  - Chuang, Chun-Yi 
AU  - Su, Chun-Wen 
AU  - Yang, Wei-En 
AU  - Tang, Chih-Hsin 
AU  - Yang, Shun-Fa 
AU  - Lin, Chiao-Wen 

TI  - Alisol A Exerts Anti-Proliferative Activity against Human Oral Cancer Cells through Triggering JNK/p38 MAPK-Mediated Apoptotic Cascade
T2  - Oncology Research

PY  - 2025
VL  - 33
IS  - 11
SN  - 1555-3906

AB  -  <b>Background:</b> Alisol A is a natural compound isolated from <i>Alismatis Rhizoma</i>, known for its diverse pharmacological activities, including anticancer and neuroprotective effects. This study aimed to explore the anticancer effects of Alisol A on oral cancer cells and elucidate its underlying mechanisms. <b>Methods:</b> Cell viability was measured by MTT assay, cell cycle by flow cytometry, and apoptosis by Annexin V/PI staining and caspase activation. Regulation of signaling pathways was analyzed using an apoptosis-related protein array, immunoblotting, and specific kinase inhibitors. <b>Results:</b> Alisol A reduced the viability of oral cancer cell lines, induced sub-G1 phase accumulation, and augmented the number of apoptotic cells. Protein array results indicated that Alisol A enhanced the expression of heme oxygenase-1 (HO-1), while suppressing cellular inhibitor of apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP) levels in SCC-9 cells. These changes were further confirmed in both SCC-9 and HSC-3 cells by immunoblotting. In addition, Alisol A triggered the activation of caspase-8, -9, and -3, as well as poly (ADP-ribose) polymerase (PARP) cleavage in both cell lines. Analysis of signaling pathways showed that mitogen-activated protein kinases (MAPKs) were significantly activated by Alisol A. Notably, inhibition of JNK and p38 markedly reduced Alisol A-induced activation of caspase-8, -9, and -3. <b>Conclusions:</b> Our findings demonstrate that Alisol A exerts potent anticancer effects on oral cancer cells by inducing caspase-dependent apoptosis via activation of the JNK and p38 signaling pathways. These results suggest that Alisol A may have therapeutic potential for the treatment of oral cancer.
KW  - Alisol A; oral squamous cancer cell; apoptosis; c-Jun N-terminal kinase; p38

DO  - 10.32604/or.2025.069877